A Next Generation Stem Cell Company - Cynata...Cynata Therapeutics Overview 28 May, 2017 3 •Australian Securities Exchange (ASX) listed biotech company developing a novel therapeutic

A Next Generation Stem Cell CompanyDr. Ross Macdonald, CEO Cynata Therapeutics LimitedMay 2017

Important Information

This presentation has been prepared by Cynata Therapeutics Limited. (“Cynata” or the “Company”) based on information available to it as at the date of this presentation. The information in this presentation is provided in summary form and does not contain all information necessary to make an investment decision.

This presentation does not constitute an offer, invitation, solicitation or recommendation with respect to the purchase or sale of any security in Cynata Therapeutics , nor does it constitute financial product advice or take into account any individual’s investment objectives, taxation situation, financial situation or needs. An investor must not act on the basis of any matter contained in this presentation but must make its own assessment of Cynata Therapeutics and conduct its own investigations. Before making an investment decision, investors should consider the appropriateness of the information having regard to their own objectives, financial situation and needs, and seek legal, taxation and financial advice appropriate to their jurisdiction and circumstances. Cynata Therapeutics is not licensed to provide financial product advice in respect of its securities or any other financial products. Cooling off rights do not apply to the acquisition of Cynata Therapeutics securities.

Although reasonable care has been taken to ensure that the facts stated in this presentation are accurate and that the opinions expressed are fair and reasonable, no representation or warranty, express or implied, is made as to the fairness, accuracy, completeness or correctness of the information, opinions and conclusions contained in this presentation. To the maximum extent permitted by law, none of Cynata Therapeutics, its officers, directors, employees and agents, nor any other person, accepts any responsibility and liability for the content of this presentation including, without limitation, any liability arising from fault or negligence, for any loss arising from the use of or reliance on any of the information contained in this presentation or otherwise arising in connection with it.

The information presented in this presentation is subject to change without notice and Cynata Therapeutics does not have any responsibility or obligation to inform you of any matter arising or coming to their notice, after the date of this presentation, which may affect any matter referred to in this presentation.

The distribution of this presentation may be restricted by law and you should observe any such restrictions.

Forward looking statements

This presentation contains certain forward looking statements that are based on the Company’s management’s beliefs, assumptions and expectations and on information currently available to management. Such forward looking statements involve known and unknown risks, uncertainties, and other factors which may cause the actual results or performance of Cynata to be materially different from the results or performance expressed or implied by such forward looking statements. Such forward looking statements are based on numerous assumptions regarding the Company’s present and future business strategies and the political and economic environment in which Cynata will operate in the future, which are subject to change without notice. Past performance is not necessarily a guide to future performance and no representation or warranty is made as to the likelihood of achievement or reasonableness of any forward looking statements or other forecast. To the full extent permitted by law, Cynata and its directors, officers, employees, advisers, agents and intermediaries disclaim any obligation or undertaking to release any updates or revisions to information to reflect any change in any of the information contained in this presentation (including, but not limited to, any assumptions or expectations set out in the presentation).

28 May, 2017 2www.cynata.com

Cynata Therapeutics Overview

328 May, 2017 www.cynata.com

• Australian Securities Exchange (ASX) listed biotech company developing a novel therapeutic stem cell (MSC) technology: CymerusTM

• Technology from University of Wisconsin - Madison: “the home of stem cells”

• World-first Phase I clinical trial commenced in GvHD; sites in UK and Australia

• Strategic partnership with Fujifilm Corporation, leading Japanese regenerative medicine company

• License option agreement with apceth GmbH & Co. KG for several disease target areas

• Strong balance sheet: cash runway into 2019 based on current projections

• Compelling preclinical data from a range of animal proof-of-concept studies

• Favorable regulatory environment with Japan, US and EU fast tracking stem cell therapies

• Broad commercial potential in a range of diseases including stroke, heart disease and osteoarthritis

Cynata Key FactsDr Paul Wotton – Chairman• Former CEO of Ocata Therapeutics (NASDAQ: OCAT) managing it through a take-

over by Astellas Pharma, in a US$379 million transaction. • Previous executive roles with Antares Pharma Inc. (NASDAQ: ATRS), Topigen

Pharmaceuticals and SkyePharma. • Member of the board of Vericel Corporation and past Chairman of the Emerging

Companies Advisory Board of BIOTEC Canada.

Cynata Therapeutics is an Australian clinical-stage biotechnology company developing disruptive regenerative medicines.

To build shareholder value through a commitment to commercialising and bringing to patients its proprietary Cymerus™ therapeutic stem cell technology.

Dr Ross Macdonald – Managing Director and Chief Executive Officer• 30 years’ experience and a track record of success in pharmaceutical and

biotechnology businesses. • Previous senior management positions with Hatchtech, Sinclair Pharmaceuticals,

Connetics Corporation (Palo Alto, CA), and Stiefel Laboratories, the largest independent dermatology company in the world and acquired by GSK in 2009 for £2.25b.

Dr Stewart Washer – Non-Executive Director• +20 years of CEO and Board experience in medical technology, biotech and

agrifood companies. • Chairman of Orthocell Ltd and Minomic International.• Previously CEO roles with Calzada (ASX:CZD), Phylogica (ASX:PYC) and Celentis

and managed the commercialisation of intellectual property from AgResearch inNew Zealand with 650 Scientists and $130m revenues.

Dr John Chiplin – Non-Executive Director• Significant international experience in the life science and technology industries.

Recent transactions include US stem cell company Medistem (acquired by Intrexon), Arana (acquired by Cephalon), and Domantis (acquired by GSK).

• Was head of the $300M ITI Life Sciences investment fund in the UK and his owninvestment vehicle, Newstar Ventures.

Mr Peter Webse – Non-Executive Director/Company Secretary• +25 years’ company secretarial experience. • Managing Director of Platinum Corporate Secretariat Pty Ltd, a company

specialising in providing company secretarial, corporate governance and corporate advisory services.

ASX code CYP

Commenced operations

November 2013

Market cap A$ ~50m

Shares on issue 90m

Cash

$ 11.6m as at 31 March 2017($10m raised in Jan 2017 via placement and Fujifilm strategic partnership)

Number of shareholders

~2300; FUJIFILM ~9%


Our Story


Strategic partnership and $4m investment from FUJIFILM

Successful evaluation of Cymerus platform by apceth

NOW...Patient dosing commenced in GvHD clinical trial….

WORLD FIRST

CymerusTM MSC platform technology developed at Wisconsin Alumni Research Foundation, a technology transfer organisation serving the University of Wisconsin–Madison

Positive pre-clinical research in Graft vs. Host Disease, Asthma, Heart Attack and Brain Cancer paving the way for clinical trials

Approval for Phase I clinical trials in the UK and Australia for GvHD

Cymerus platform successfully validated as a GMP manufacturing process

NEXT...Exercise of license option agreement with FUJIFILM with US$3m fee PLUS ~A$60m in milestones PLUS double digit royalties thereafter

License option agreement with apceth

The Market


Global regenerative medicine market was worth $18.9 billion in 2016 and will grow to over $53.7 billion by 20211

Stem cells are the cornerstone of contemporary regenerative medicine applications2

Sources: 1. Research and Markets - Global Regenerative Medicine Market Analysis & Forecast. 2. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008

“

Mesenchymal stem cells (MSCs) have broad therapeutic potential − Cynata is presently focussing on several exciting opportunities:

Source: 1. GBI Research. 2. GlobalData 3. GrandViewResearch 4. GrandViewResearch 5. WHO

Disease Target Areas

Graft v Host Disease (GvHD) – a common complication that can occur after bone marrow or organ transplants. A half a billion dollar market by 2021.

Cardiovascular disease (Heart Failure, Heart Attack and Acute Coronary Syndrome ACS) - The global market for Cardiovascular Disease (CVD) is expected to grow to US$18.2 billion by 20191

Pulmonary diseases -Pulmonary fibrosis/scarring of the lungs expected to be US$3.2b by 20252 and asthma that affects 1 in every 12 people reaching U$25b by 20243

Brain Cancer / Glioblastoma (engineered MSCs) – In 2012, 14 million new cases of cancer and about 8.2 million deaths were reported5. The market is estimated to be worth US$773.1 million by 20254


https://www.thepharmaletter.com/article/idiopathic-pulmonary-fibrosis-market-set-to-grow-to-3-2-billion-by-2025-report

http://www.grandviewresearch.com/press-release/global-asthma-therapeutics-market

http://www.grandviewresearch.com/industry-analysis/brain-tumor-diagnosis-and-therapeutics-market

GvHD − A Growing Market

• Graft-versus-host disease (GvHD) occurs after a bone marrow or stem cell transplant from a donor

• This is an allogeneic transplant vs. an autologous transplant (when a patient receives their own stem cells)

• The transplanted cells regard the recipient's body as foreign and reject and attack the recipient's body

• There has been a large increase in prevalence and severity over the past two decades due to medical advances in stem cell therapies


Sources: 1. QIMR Berghofer Medical Research Institute 2. Vision Gain 3. Leukaemia Foundation 4. Bone Marrow Donors Worldwide (BMDW) and the World Marrow Donor Association (WMDA)

Stem cell transplants worldwide 3

International Marrow Donor Registries and

Potential Donors 4

GvHD occurs in up to 70 per cent of patients receiving stem cell

transplant to treat blood cancer1

market value for the treatment of GvHD2

by 2021

FUJIFILM’s projections for the GvHD market show peak revenues of US$300m p.a. which would result in >US$30m per year in royalties for Cynata

1 million

25 million 70% $0.51bn

http://www.qimrberghofer.edu.au/2017/04/immune-cell-discovery-opens-possibility-new-treatment-deadly-disease/

mailto:https://www.visiongain.com/Report/1794/Global-Graft-versus-Host-Disease-(GVHD)-Market-2017-2027,

http://www.fcarreras.org/en/a-total-of-1-million-stem-cell-transplants-have-been-performed-worldwide_147898

https://bethematch.org/news/news-releases/international-marrow-donor-registries-reach-25-million-potential-donors--give-hope-to-searching-blood-cancer-patients-around-the-world/

About Stem Cells and the Platform


Sources: 1. Research and Markets -Global Regenerative Medicine Market Analysis & Forecast

How the Cymerus MSC platform works and overcomes the inherent challenges facing MSC therapies today.

Why MSCs?

What are MSCs?

• Mesenchymal stem cells (MSCs) are adult stem cells found in bone marrow and certain other tissues.

What do they do?

• They have the ability to self renew.

• They secrete bioactive molecules and have immunosuppressive and immunoregulatory properties – giving them enormous therapeutic potential.

How much commercial interest is there?

Over 650 clinical trials investigating the efficacy of MSCs in treating diseases have been initiated.1

Promising results have been shown in conditions such as heart attack, stroke, GvHD, Crohn's disease, multiple sclerosis, osteoarthritis and diabetes complications


Source: 1. www.clinicaltrials.gov

CD4+ T Lymphocyte CD8+ T Lymphocyte

NK Cell

Dendritic Cell

MonocyteNeutrophil

IL-6

HLA-G5

PGE2

FoxP3+ T Reg

ϒδ T Cell

HLA-G5IDO, iNOS, HO1

TGFβ, HGF, PGE2

PGE2

PGE2

MSC

How Are MSCs Manufactured?

First generation methods require many tissue donors and massive cell expansion (i.e., multiply) to manufacture sufficient product.

First generation methods pose a number of key challenges for the manufacture of MSC medicines….


Cynata’s Cymerus platform overcomes each of these challenges by using induced pluripotent stem cells (iPSCs) that are more easily derived from a single blood donation

Source: 1. www.clinicaltrials.gov

Cynata’s patented process uses iPSCs to manufacture MSCs

Issues with production scale-

up

1

Inconsistent product quality

2

Reduced product efficacy

3

Significant intra-and inter- donor

variability

4

Recruitment and qualification of

donors is costly and time consuming

5

Cynata process for sourcing and manufacturing therapeutic MSCs

Cymerus Platform vs First Generation ProcessCynata’s Cymerus platform enables MSCs to be manufactured effectively and efficiently by

eliminating the need to use multiple donors, multiple times.


*iPSCs are derived from e.g. blood cells and have been reprogrammed back into an embryonic-like state that enables the development of an unlimited source of virtually any type of human cell.”

Cells donated from one donor, one time via a

simple blood donation

Cells are re-programmed to derive induced

pluripotent stem cells (iPSCs*)

Therapeutic MSCs are administered to

the patient

Cymerus platform harnesses unlimited

expansion capacity of iPSCs

Induction of precursor cells

Differentiation toMSCs and packaging

Generation of precursor cell colonies

(mesenchymoan-gioblasts) (MCA)

First generation process for sourcing and manufacturing therapeutic MSCs

Cells donatedfrom multiple

donors, multiple times

Therapeutic MSCs are administered

to the patient

Finished product prepared and

packaged

Purified MSCs are then massively

expanded to provide sufficient quantities

MSCs are isolated from other cell

types in the sample

CymerusTM

Patented process uses iPSCs to manufacture

MSCs

Donation taken through a complex surgical procedure

Development Progress and Validation



Phase I Clinical trial in GvHD: patient dosing commenced.

Strategic partnership and license option agreement with FUJIFILM Corporation.

Development Progress

Pre-Clinical Phase 1 Phase 2 Phase 3 Evidence

GvHDPatient dosing commenced

Pre-clinical research with University of Massachusetts shown Cymerus™ MSCs to be highly effective in GvHD: CYP-001 treatment substantially prolonged survival in an animal model

Asthma

Cymerus™ MSCs demonstrated significant beneficial effects on three key components of asthma: airway hyper-responsiveness, inflammation and airway remodeling.

Heart Attack

Preliminary results from pre-clinical trials suggests that Cymerus™ iPSC-generated MSCs may have the potential to restore cardiac function and reduce scar size after a heart attack.

Cancer / Glioblastoma

Research collaboration in genetically modified MSCs in cancer: involves modifying stem cells to target cancer

University of Massachusetts

University of Sydney

Harvard/MGH

Monash University

Scalable manufacture of MSCs without reliance upon multiple donors

First clinical trial of an allogeneic, iPSC-derived MSC product

World firsts:


Next Steps with Fujifilm

License option agreement for further development and commercialisation of Cynata’s MSCs for GvHD

License option agreement

• Exclusive license option with Fujifilm for GvHD

Phase 1

• Phase 1 clinical trial commenced

• Expected completion: end 2017

Exercise of Fujifilm option

• Any time up to 90 days after completion of Phase 1 trial.

• Upfront US$3 million milestone payment

Phase 2 and beyond

• Fujifilm responsible for further development activities and costs

• Fujifilm to pay Cynata agreed milestones ($60m+) and double-digit royalties on product sales


External collaborations: preclinical PoC development of potential products for

target diseases

Business Model

Early Revenue Streams

Upfront Option/License payments From pharma/biotech for licensing of CymerusTM

platform

Milestone payments From partners as products progress through clinical trials and approval

Royalties From partner revenue of marketed products

✓ GvHD/transplantation✓ Asthma/respiratory disease✓ Heart Attack✓ Cancer/Glioblastoma

✓ GvHD option license agreement with Fujifilm – Phase I trial now recruiting patients

Vigorous partner engagement to produce upfront payments:

option/license agreements with pharma and biotech partners for clinical development (Phase 1, 2 & 3),

registration and sale

Further revenues through milestone payments plus royalties on marketed

products

✓ Successful trial of Cymerus platform with apceth and license option agreement in place


Validation and Outlook


• Positive results from pre-clinical trials in the treatment of GvHD, asthma, heart attack and limb ischaemia – further pre-clinical research in cancer and Acute Respiratory Distress Syndrome (ARDS)

• Approval from the UK and Australia: Phase I clinical trial commenced in GvHD (world first); safety data base will facilitate further disease targets

• $4 million strategic investment from Fujifilm Corporation, leading Japanese regenerative medicine company

• License option agreement with Fujifilm for GvHD to be exercised any time up until 90 days after the trial completion – worth up to $60m in license payments plus royalties

• Successful evaluation of the Cymerus platform in apceth’s systems demonstrating ability to integrate Cymerus with other technologies giving a broader cell therapy applications for the platform

• License option agreement with apceth for several disease target areas

• Favourable regulatory environment with Japan, US and EU accelerating legislative changes to accelerate stem cell therapy research and uses

Market Activity and Investment Summary



Regenerative medicine and stem cell market highly active with a flurry of M&A and investment in recent years.

Market Activity


Cord Blood Registry Acquired by AMAG

Pharmaceuticals Inc2015

USD700M

Bayer and Versant Ventures launched stem

cell therapy company BlueRock Therapeutics

2016

USD225M

(SERIES A)

Ocata Therapeutics (Acquired by Astellas

2016

USD379M

Cellular DynamicsAcquired by Fujifilm

2015

USD307M

Novoheart HoldingsWoodrose Ventures to

acquire 2017

USD20M

CiRA & Takeda partner in iPS Collaboration

2015

USD267M

A significant number of licence agreements have also been secured over recent years

• Only company in the world with technology for mass-production

of therapeutic MSCs of consistent quality and without reliance on

multiple donors

• Cynata’s Cymerus™ technology overcomes the challenges

inherent in first generation production methods by

industrialising the production of MSCs

• Compelling data in pre-clinical studies for the treatment of

asthma, CLI, heart attack and GvHD

• Regenerative medicine market expected to grow to US$170bn1

by 2020 and an active investment area for pharmaceutical

companies, including Astellas, J&J and Fujifilm

• License-driven business model with license option agreements in

place with Fujifilm and apceth producing early revenues

• Experienced management team

• Strong academic partnerships

• Value-accretive news flow expected in near term

Investment Summary

Source: 1. Grand View Research Report published Sept 2015 http://www.grandviewresearch.com/industry-analysis/stem-cells-market


http://www.grandviewresearch.com/industry-analysis/stem-cells-market

Thank you for your attention

Cynata Therapeutics LimitedSuite 11233 High StreetArmadaleVictoria 3143

Contact details:

[email protected]

+61 (0) 412 119343

www.cynata.com


Documents

A Next Generation Stem Cell Company - Cynata...Cynata Therapeutics Overview 28 May, 2017 3 •Australian Securities Exchange (ASX) listed biotech company developing a novel therapeutic